雄性生殖细胞特异蛋白102P介导组蛋白泛素化修饰调控第一次减数分裂的分子机制研究

世界范围内不孕不育在育龄夫妇中约占10-15%。其中男性和女性因素各约占50%。临床上根据男性不育患者输精管阻塞情况将无精症分为阻塞性无精子症和非阻塞性无精子症。但由于NOA无成熟的精子产生，而且NOA的病因复杂，临床上仍无有效的治疗措施。目前发现导致NOA的因素主要包括遗传学因素、内分泌因素等。减数分裂缺陷是生殖细胞发育的主要障碍之一。目前对于雄、雌生殖细胞减数分裂的机制研究已成为当前及未来生殖医学研究的热点问题。目前包括本实验室在内的国内外研究团队已鉴定出多个参与生殖细胞减数分裂调控的蛋白。本项目正是基于前期测序筛选生殖细胞特异表达基因的工作基础，对于我们鉴定的一个雄性生殖细胞特意表达的基因102P进行深入系统的功能性研究。我们拟利用102P基因功能缺失小鼠模型，揭示102P在第一次减数分裂前期中对染色体行为的影响和作用机制，从而加深对减数分裂分子机制的理解和临床诊疗的应用。

About 10-15% of couples world-wide suffer from infertility, in which male and female factors account for 50%, respectively. In male infertility, azoospermia is one of the leading causes and it can be classified into obstructive azoospermia (OA) or non-obstructive azoospermia (NOA) based on histo-pathological characteristics. However, because there is a lack of mature sperm production in NOA, and etiologies of NOA is usually complicated, there is still no available effective treatment in clinics. Factors that are reported to be involved in NOA including genetic factors, endocrine factors, and infections. Among them, about 75% are caused by genetic factors. With second-generation sequencing and the wide use of transgenic mice in reproductive medicine research, studies of meiotic mechanisms underlying core events of male spermatogenesis have become a hot topic. Various research teams including our group have identified proteins involved in the regulation of meiosis. The aim of this project is to study the mouse male germ cell-specific gene 102P based on previous RNA sequencing. The 102P knockout mouse model will be used to reveal roles of 102P in chromosomal behaviors during meiosis prophase I using molecular and biochemical methods. By studying mechanisms of 102P action, we will improve the understanding of molecular mechanisms of meiosis and provide a knowledge basis for clinical diagnosis and treatment of NOA.